Withania somnifera prevents acquisition and expression of morphine-elicited conditioned place preference

Abstract

Previous studies have reported that some of the central effects of morphine are counteracted by the administration of the methanolic extract of the root of Indian ginseng, Withania somnifera Dunal (WSE). The present study sought to determine whether WSE affects acquisition and expression of morphine-elicited conditioned place preference (CPP) in CD-1 mice. In CPP acquisition experiments, WSE (0, 25, 50, and 100 mg/kg) was administered, during conditioning, 30 min before morphine (10 mg/kg), whereas in expression experiments, WSE (0, 25, 50, and 100 mg/kg) was administered 30 min before the postconditioning test. The results demonstrate (i) that WSE was devoid of motivational properties; (ii) that WSE (100 mg/kg) was devoid of effects on spontaneous and morphine-stimulated motor activity and on spatial memory; and (iii) that WSE (50 and 100 mg/kg) significantly prevented the acquisition and expression of CPP. Further, to characterize the receptor(s) involved in these effects, we studied, by receptor-binding assay, the affinity of WSE for µ-opioid and γ-aminobutyric acid B receptors. These experiments revealed a higher affinity of WSE for γ-aminobutyric acid B than for µ-opioid receptors. Overall, these results point to WSE as an interesting alternative tool, worthy of further investigation, to study opiate addiction.

Effects of Withania somnifera on oral ethanol self-administration in rats

“…Accordingly, evidence has been provided in support of the involvement of the endogenous opioid system in the acute effects of ethanol (Pastor et al, 2011;Mitchell et al, 2012) and of the role that opioid antagonists play experimentally, in the behavioural effects of ethanol (Ciccocioppo et al, 2002;Heyser et al, 2003;Ji et al, 2008), and clinically, in the treatment of alcoholism (Foa et al, 2013;Van den Brink et al, 2013). Hence, in light of the above evidence and, in particular, of the ability of WSE to affect the conditioned positive incentive value of morphine-associated contexts (Ruiu et al, 2013), the aim of the present study was to investigate, in rats, the effects of WSE on oral ethanol self-administration (acquisition, maintenance and breakpoint, as well as deprivation effect and reinstatement of seeking behaviours).…”

“…Furthermore, chronic administration of WSE has been reported to protect from the loss of dendritic spines that occurs in the shell of nucleus accumbens upon morphine withdrawal in morphine-dependent rats (Kasture et al, 2009). More recently, it has also been shown that WSE prolongs morphine-induced analgesia , prevents the development of morphine-induced rebound hyperalgesia and the acquisition and expression of morphine-elicited conditioned place preference, possibly through a GABA B receptor-mediated mechanism (Ruiu et al, 2013). Notably, W. somnifera or its preparation may also reduce ethanol withdrawal-induced anxiety and potentiate ethanol-induced anxiolysis (Gupta and Rana, 2008).…”

“…Therefore, to envisage the possible involvement of GABA B receptors, suggested previously in the effects of WSE on morphine-elicited conditioned place preference (Ruiu et al, 2013), we also aimed to study the effects of baclofen on ethanol self-administration and the effects of phaclofen, a competitive GABA B receptor antagonist (Kerr et al, 1987), on the ability of WSE (and baclofen) to affect motivation to self-administer ethanol.…”

Novel diazabicycloalkane delta opioid agonists

“…Ligand binding assays were carried out according to the procedure described by Ruiu et al 48 Briefly, the whole brain minus cerebellum was homogenised with Polytron in 50 volumes (w/v) of 50 mM Tris-HCl (pH 7.4), centrifuged at 48,000g for 20 min at 4°C, re-suspended in 50 volumes of the same buffer solution, and incubated at 37°C for 45 min. After a further centrifugation step at 48,000g for 20 min at 4°C, the final pellet was re-suspended in the same buffer solution.…”

“…The affinities of the novel compounds for the l, d, and j opioid receptors were determined through radioligand binding assays by adopting previously reported procedures, 48 To investigate intrinsic activity of compounds 3-7, in vitro tests aimed to evaluate phosphorylated ERK 1/2 (P-ERK 1/2) regulation elicited by the novel derivatives on neuroblastoma  glioma NG108-15 hybrid cells were carried out. 50 In fact, it has been ascertained that NG108-15 hybrid cells express d, but not l or j receptors.…”